[논문]Safety data on 19 vehicles for use in 1 month oral rodent pre‐clinical studies: administration of hydroxypropyl‐ß‐cyclodextrin causes renal toxicity

Healing, Guy; Sulemann, Tabassum; Cotton, Peter; Harris, Jayne; Hargreaves, Adam; Finney, Rowena; Kirk, Sarah; Schramm, Carolin; Garner, Clare; Pivette, Perrine; Burdett, Lisa

doi:10.1002/jat.3155

Safety data on 19 vehicles for use in 1 month oral rodent pre‐clinical studies: administration of hydroxypropyl‐ß‐cyclodextrin causes renal toxicity

Journal of applied toxicology : JAT, v.36 no.1, 2016년, pp.140 - 150

Healing, Guy (AstraZeneca, Drug Safety and Metabolism, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK) , Sulemann, Tabassum (AstraZeneca, Pharmaceutical Development, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK) , Cotton, Peter (AstraZeneca, Drug Safety and Metabolism, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK) , Harris, Jayne (AstraZeneca, Drug Safety and Metabolism, 310 Darwin Building, Science Park, Cambridge, CB40 0WG, UK) , Hargreaves, Adam (AstraZeneca, Drug Safety and Metabolism, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK) , Finney, Rowena (AstraZeneca, Drug Safety and Metabolism, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK) , Kirk, Sarah (AstraZeneca, Discovery Sciences, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK) , Schramm, Carolin (Ast) , Garner, Clare , Pivette, Perrine , Burdett, Lisa

Abstract ▼ AI-Helper

AbstractPotential new drugs are assessed in pre‐clinical in vivo studies to determine their safety profiles. The drugs are formulated in vehicles suitable for the route of administration and the physicochemical properties of the drug, aiming to achieve optimal exposure in the test species. The availability of safety data on vehicles is often limited (incomplete data, access restricted/private databases). Nineteen potentially useful vehicles that contained new and/or increased concentrations of excipients and for which little safety data have been published were tested. Vehicles were dosed orally once daily to HanWistar rats for a minimum of 28 days and a wide range of toxicological parameters were assessed. Only 30% (w/v) hydroxypropyl‐ß‐cyclodextrin was found unsuitable owing to effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased salivation and hence this vehicle should be used with caution. As 40% (v/v) tetraethylene glycol affected urinary parameters, its use should be carefully considered, particularly for compounds suspected to impact the renal system and studies longer than 1 month. There were no toxicologically significant findings with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v) Miglyol®812, 20% (w/v) Kolliphor®RH40, 10% (w/v) Poloxamer 407, 5% (w/v) polyvinylpyrrolidone K30 or 10% (v/v) Labrafil®M1944. All other vehicles tested caused isolated or low magnitude effects which would not prevent their use. The aim of sharing these data, including adverse findings, is to provide meaningful information for vehicle selection, thereby avoiding repetition of animal experimentation. Copyright © 2015 John Wiley & Sons, Ltd.

주제어

참고문헌 (38)

Anonymous . 1987 . Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myristic acid, and stearic acid . J. Am. Coll. Toxicol. 6 : 321 – 401 .
Brewster MA , Loftsson T . 2007 . Cyclodextrins as pharmaceutical solubilizers . Adv. Drug Deliver. Rev. 59 : 645 – 666 .
Delongeas JL , Vermeil de Conchard G , Beamonte A , Bertheux H , Spire C , Maisonneuve C , Becourt‐Lhote N , Goldfain‐Blanc F , Claude N . 2010 . Assessment of Labrasol®/Labrafil®/Transcutol® (4/4/2, v/v/v) as non‐clinical vehicle for poorly water‐soluble compounds after 4‐weeks oral toxicity study in Wistar rats . Regul. Toxicol. Pharm. 57 : 284 – 290 .
Duvinage C , Millecamps S , Sagnier A , Guffroy M , Sarsat J‐P , Belin V . 1996 . One‐month intravenous toxicity studies of poloxamer 188 in male Sprague‐Dawley rats and in beagle dogs . Toxicol. Lett. 88 : 101 .

상세보기
European Medicines Agency (EMA) . Committee for Medicinal Products for Human Use (CHMP). 2013 . Guideline on the Use of Phthalates as Excipients in Human Medicinal Products – Draft . EMA/CHMP/SWP/362974/2012.
Gad SC , Cassidy CD , Aubert N , Spainhour B , Robbe H . 2006 . Nonclinical vehicles use in studies by multiple routes in multiple species . Int. J. Toxicol. 25 : 499 – 521 .
Gad SC . 2009 . Appendix E: Common vehicles for nonclinical evaluation of therapeutic agents . In Drug Safety Evaluation , 2nd edn , Gad SC (ed). John Wiley and Sons : New York ; 1140 – 1160 .
Gopinathan S , O'Neill E , Rodriguez LA , Champ R , Phillips M , Nouraldeen A , Wendt M , Wilson AGE , Kramer JA . 2013 . In vivo toxicology of excipients commonly employed in drug discovery in rats . J. Pharm. Toxicol. Methods. 68 : 284 – 295 .
Gould S , Scott R . 2005 . Hydroxypropyl‐beta‐cyclodextrin: A toxicology review . Food Chem. Toxicol. 43 : 1451 – 1459 .
Hamid KA , Katsumi H , Sakane T , Yamamoto A . 2009 . The effects of common solubilising agents on the intestinal membrane barrier functions and membrane toxicity in rats . Int. J. Pharmaceutics 379 : 100 – 108 .
Hermansky SJ , Neptun DA , Loughran KA , Leung HW . 1995 . Effects of polyethylene glycol 400 (PEG 400) following 13 weeks of gavage treatment in Fischer‐344 rats . Fd. Chem. Toxic. 33 : 139 – 149 .
Humberstone AJ , Charman WN . 1997 . Lipid‐based vehicles for the oral delivery of poorly soluble drugs . Adv. Drug Deliver. Rev. 25 : 103 – 128 .
ICH M3(R2) . 2009 . Non‐Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals .
Kitagawa H , Yano H , Fukuda Y . 1973 . Chronic toxicity of hydroxypropylmethylcellulose phthalate in rats . Pharmacometrics 7 : 689 – 701 .
LaKind JS , McKenna EA , Hubner RP , Tardiff RG . 1999 . A review of the comparative mammalian toxicity of ethylene glycol and propylene glycol . Cr. Rev. Toxicol. 29 : 331 – 365 .
Leuner C , Dressman J . 2000 . Improving drug solubility for oral delivery using solid dispersions . Eur. J. Pharm. Biopharm. 50 : 47 – 60 .

상세보기
Li P , Zhao L , Yalkowsky SH . 1999 . Combined effect of co solvent and cyclodextrin on solubilization of nonpolar drugs . J. Pharm. Sci. 88 : 1107 – 1111 .
Loftsson T , Másson M , Brewster , ME . 2004 . Self‐association of cyclodextrins and cyclodextrin complexes . J. Pharm. Sci. 93 : 1091 – 1099 .

상세보기
Lowry OH , Rosebrough NJ , Farr AL , Randall RJ . 1951 . Protein measurement with the folin phenol reagent . J. Biol. Chem. 193 : 265 – 275 .
MAK Value Documentation . 1998 . The MAK collection for occupational health and safety: Polyethylene glycol . In Occupational Toxicants . Vol. 10 , Wiley‐KH, Weinheim : Germany ; 248 – 270 DOI: 10.1002/3527600418.mb2532268kske0010 .
MAK Value Documentation . 2002 . The MAK Collection for Occupational Health and Safety: Oleic Acid . Wiley‐KH, Weinheim : Germany ; 246 – 266 DOI: 10.1002/3527600418.mb11280kske0017 .
McMartin K. 2009 . Are calcium oxalate crystals involved in the mechanism of acute renal failure in ethylene glycol poisoning? Clin. Toxicol. (Phila.) 47 : 859 – 869 .
Mullertz A , Ogbonna A , Ren S , Rades T . 2010 . New perspectives on lipid and surfactant based drug delivery systems for oral delivery of poorly soluble drugs . J. Pharm. Pharmacol. 62 : 1622 – 1636 .

상세보기
Noel PRB , Barnett KC , Davies RE , Jolly DW , Leahy JS , Mawdesley‐Thomas LE , Shillam KWG , Swuires SPF , Street AE , Tucker WC , Worden AN . 1975 . The toxicity of dimethyl sulphoxide (DMSO) for the dog, pig, rat and rabbit . Toxicology 3 : 143 – 169 .

상세보기
Pestel S , Martin H‐J , Maier G‐M , Guth B . 2006 . Effect of commonly used vehicles on gastrointestinal, renal and liver function in rats . J. Pharmacol. Toxicol. Methods 54 : 200 – 214 .

상세보기
Pomara C , Fiore C , E'Errico S , Riezzo I , Fineschi V . 2008 . Calcium oxalate crystals in acute ethylene glycol poisoning: A confocal laser scanning microscope study in a fatal case . Clin. Toxicol. (Phila.) 46 : 322 – 324 .
Schladt L , Ivens I , Karbe E , Ruhl‐Fehlert C , Bomhard E . 1998 . Subacute oral toxicity of tetraethylene and ethylene glycol administered to Wistar rats . Exp. Toxic. Pathol. 50 : 257 – 265 .
Schwarz W . 1990 . PVP: A Critical Review of the Kinetics and Toxicology of Polyvinylpyrrolidone (povidone) . CRC Press .
Sellers RS , Antman M , Phillips J , Khan KN , Furst SM . 2005 . Effect of miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/twen 80 . Drug Chem. Toxicol. 28 : 423 – 432 .
Singh‐Joy SD . 2008 . Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 288, 331, 333, 334, 335, 338, 401, 402, 403 and 407, poloxamer 105 benzoate and poloxamer 182 dibenzoate as used in cosmetics . Int. J. Toxicol. 27 : 93 – 128 .
Som I , Bhatia K , Yasir M . 2012 . Status of surfactants as penetration enhancers in transdermal drug delivery . J. Pharm. Bioallied. Sci. 4 : 2 – 9 .
Stella VJ , Rajewski RA . 1997 . Cyclodextrins: their future in drug formulation and delivery . Pharm. Res. 14 : 556 – 567 .

상세보기
Stokes AH , Kemp DC , Faiola B , Jordan HL , Merrill CL , Hailey JR , Brown RE , Bailey DW . 2013 . Effects of Solutol (Kolliphor) and Cremophor in Polyethylene Glycol 400 vehicle formulation in Sprague‐Dawley rats and beagle dogs . Int. J. Toxicol. 32 : 189 – 197 .
Strickley RG . 2004 . Solubilizing excipients in oral and injectable formulations . Pharm. Res. 21 : 201 – 230 .

상세보기
Sullivan Jr DW , Gad SC , Julien M . 2014 . A review of the nonclinical safety of Transcutol®, a highly purified form of diethylene glycol monoethyl ether (DEGEE) used as a pharmaceutical excipient . Food Chem. Toxicol. 72 : 40 – 50 .

상세보기
Sweetana S , Akers MJ . 1996 . Solubility principles and practices for parenteral drug dosage form development . PDA J. Pharm. Sci. Technol. 50 : 330 – 342 .

상세보기
Thackaberry EA , Kopytek S , Sherrat P , Trouba K , McIntyre B . 2010 . Comprehensive investigation of hydroxypropyl methylcellulose, propylene glycol, polysorbate 80 and hydroxypropyl‐beta‐cyclodextrin for use in general toxicology studies . Toxicol. Sci. 117 : 485 – 492 .

상세보기
Thackaberry EA . 2013 . Vehicle selection for nonclinical oral safety studies . Expert Opin. Drug Metab. Toxicol. 9 : 1635 – 1646 .

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증

Safety data on 19 vehicles for use in 1 month oral rodent pre‐clinical studies: administration of hydroxypropyl‐ß‐cyclodextrin causes renal toxicity

Abstract ▼ AI-Helper

주제어

참고문헌 (38)

이 논문을 인용한 문헌

관련 콘텐츠

원문 URL 링크

연관된 기능

이 논문과 함께 이용한 콘텐츠

AI-Helper ※ AI-Helper는 오픈소스 모델을 사용합니다.

선택된 텍스트